文章基本信息

标题：Pharmaceutical Approach to HIV Protease Inhibitor Atazanavir for Bioavailability Enhancement Based on Solid Dispersion System
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作者：Keizo Fukushima ; Shuichi Terasaka ; Kenta Haraya 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2007
卷号：30
期号：4
页码：733-738
DOI：10.1248/bpb.30.733
出版社：The Pharmaceutical Society of Japan
摘要：Atazanavir (ATV) is a low oral bioavailability (BA) compound and, clinically, is generally coadministrated with ritonavir (RTV), which boosts the oral BA of ATV by inhibiting cytochrome P450 (CYP) 3A, and P-glycoprotein (Pgp) via the same metabolic pathway. However, depending on pharmacokinetic interaction, RTV-boosted ATV has great potential for other comedication. In this study we demonstrated the pharmaceutical approach to BA improvement of ATV without RTV in rats, based on the solid dispersion system using sodium lauryl sulfate (SLS) as a carrier and Gelucire^® 50/13 as an absorption enhancer. ATV solid dispersions in SLS were prepared by a conventional solvent method and, at ratios of ATV to SLS of 1 : 2 and 1 : 3, were demonstrated to form an amorphous state in powder X-ray diffraction (PXRD) analysis and exhibited 2.26- and 2.36-fold improvement in a dissolution test in comparison to bulk ATV, respectively. After oral administration to rats, ATV solid dispersion in SLS at a ratio of 1 : 2 showed a 3.5-fold increase in BA compared with bulk ATV. Moreover, the addition of Gelucire 50/13 to ATV solid dispersion, at a total ratio of Gelucire 50/13, ATV and SLS 1 : 1 : 2 gave 7.0- and 4.7-fold increase in C _max and BA compared with bulk ATV, respectively, when the relative BA to RTV-boosted ATV reached 93%. The results in this study proved that a pharmaceutical approach could improve the bioavailability of ATV without pharmacokinetic interaction with RTV.
关键词：atazanavir;solid dispersion;sodium lauryl sulfate;gelucire 50/13;ritonavir;powder X-ray diffraction